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Journal of Cardiovascular Pharmacology and Therapeutics, Vol. 11, No. 1, 31-45 (2006)
DOI: 10.1177/107424840601100103

Subcellular Remodeling as a Viable Target for the Treatment of Congestive Heart Failure

Naranjan S. Dhalla, PhD, MD, DSc

Department of Physiology, Faculty of Medicine; Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, 351 Tache Avenue, Winnipeg, Manitoba, R2H 2A6 Canada; nsdhalla{at}sbrc.ca

Melissa R. Dent, MSc

Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre; Department of Physiology, Faculty of Medicine

Paramjit S. Tappia, PhD

Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, and Department of Physiology, Faculty of Medicine, Winnipeg, Canada; Department of Human Nutritional Sciences, Faculty of Human Ecology, Department of Human Anatomy and Cell Science, Faculty of Medicine, University of Manitoba, Winnipeg, Canada

Rajat Sethi, PhD

Irma Lerma Rangel College of Pharmacy, Texas A&M University, Kingsville, TX

Judit Barta, MD, PhD

Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, and Department of Physiology, Faculty of Medicine

Ramesh K. Goyal, PhD

L.M. College of Pharmacy, Department of Pharmacology, Ahmedabad, India

It is now well known that congestive heart failure (CHF) is invariably associated with cardiac hypertrophy, and changes in the shape and size of cardiomyocytes (cardiac remodeling) are considered to explain cardiac dysfunction in CHF. However, the mechanisms responsible for the transition of cardiac hypertrophy to heart failure are poorly understood. Several lines of evidence both from various experimental models of CHF and from patients with different types of CHF have indicated that the functions of different subcellular organelles such as extracellular matrix, sarcolemma, sarcoplasmic reticulum, myofibrils, mitochondria, and nucleus are defective. Subcellular abnormalities for protein contents, gene expression, and enzyme activities in the failing heart become evident as a consequence of prolonged hormonal imbalance, metabolic derangements, and cation maldistribution. In particular, the occurrence of oxidative stress, development of intracellular Ca2+ overload, activation of proteases and phospholipases, and alterations in cardiac gene expression result in changes in the biochemical composition, molecular structure, and function of different subcellular organelles (subcellular remodeling). Not only does subcellular remodeling appear to be intimately involved in the transition of cardiac hypertrophy to heart failure, the mismatching of the function of different subcellular organelles leads to the development of cardiac dysfunction. Although blockade of the renin-angiotensin system, sympathetic nervous system, and various other hormonal actions have been reported to produce beneficial effects on cardiac remodeling and heart dysfunction in CHF, the actions of various cardiac drugs on subcellular remodeling have not been examined extensively. Some recent studies have indicated that both the angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists attenuate changes in sarcolemma, sarcoplasmic reticulum, and myofibril enzyme activities, protein contents, and gene expression, and partly improve cardiac function in the failing hearts. It is suggested that subcellular remodeling is an excellent target for the development of improved drug therapy for CHF. Furthermore, extensive studies should investigate the effects of different agents individually or in combination on reverse subcellular remodeling, cardiac remodeling, and cardiac dysfunction in various experimental models of CHF.

Key Words: congestive heart failure • cardiac remodeling • subcellular remodeling • cardiac drugs • cardiac hypertrophy • cardiac dysfunction

References

  • Dhalla NS, Afzal A, Beamish RE, et al. Pathophysiology of cardiac dysfunction in congestive heart failure. Can J Cardiol 9: 873–887, 1993[ISI][Medline] [Order article via Infotrieve]
  • Baig MK, Mahon N, McKenna WJ, et al. The pathophysiology of advanced heart failure. Am Heart J 135: S216–S230, 1998[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Piano MR, Bondmass M, Schwertz DW. The molecular and cellular pathophysiology of heart failure. Heart Lung 27:3–19, 1998[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Alpert NR, Mulieri LA, Warshaw D. The failing human heart. Cardiovasc Res 54:1–10, 2002[Free Full Text]
  • Cohn JN, Ferrari R, Sharpe N. Cardiac remodeling-concepts and clinical implications: A consensus paper from an international forum on cardiac remodeling. J Am Coll Cardiol 35:569–582, 2000[Abstract/Free Full Text]
  • Dhalla NS, Temsah RM, Netticadan T. Role of oxidative stress in cardiovascular diseases. J Hyperten 18:655–673, 2000[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Hasenfuss G. Animal models of human cardiovascular disease, heart failure and hypertrophy. Cardiovasc Res 39:60–76, 1998[Abstract/Free Full Text]
  • Ortega Mateo A, De Artinano AA. Highlights on endothelins: A review. Pharmacol Res 36:339–351, 1997[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Deten A, Volz HC, Briest W, et al. Differential cytokine expression in myocytes and non-myocytes after myocardial infarction in rats. Mol Cell Biochem 242:47–55, 2003[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Delcayre C, Swynghedauw B. Molecular mechanisms of myocardial remodeling. The role of aldosterone. J Mol Cell Cardiol 34:1577–1584, 2002[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Rouleau JL. The neurohormonal hypothesis and the treatment of heart failure. Can J Cardiol 12 (Suppl): 3F-8F, 1996
  • Grossman W. Cardiac hypertrophy: Useful adaptation or pathologic process? Am J Med 69:576–584, 1980[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Weber KT, Sun Y, Guarda E. Structural remodeling in hypertensive heart disease and the role of hormones. Hypertension 23:869–877, 1994[Abstract/Free Full Text]
  • Packer M. The neurohormonal hypothesis: A theory to explain the mechanism of disease progression in heart failure. J Am Coll Cardiol 20:248–254, 1992[Abstract]
  • Francis GS, Benedict C, Johnstone DE, et al. Comparison of neuroendocrine activation in patients with left ventricular dysfunction with and without congestive heart failure. A substudy of the studies of left ventricular dysfunction (SOLVD). Circulation 82:1724–1729, 1990[Abstract/Free Full Text]
  • Francis G, Goldsmith SR, Levine TB, et al. The neurohu-moral axis in congestive heart failure. Ann Intern Med 101:370–377, 1984[ISI][Medline] [Order article via Infotrieve]
  • DiBiano R The changing syndrome of heart failure: An annotated review as we approach the 21st century. J Hypertension 12 (Suppl 4):S73–S87, 1994
  • Pfeffer MA, Braunwald E. Ventricular remodeling after myocardial infarction. Experimental observations and clinical implications. Circulation 81:1161–1172, 1990[Abstract/Free Full Text]
  • Weber KT, Brilla CG. Pathological hypertrophy and cardiac interstitium. Fibrosis and renin-angiotensin-aldosterone system. Circulation 83:1849–1865, 1991[Abstract/Free Full Text]
  • Sabbah HN, Goldstein S. Ventricular remodeling: Consequences and therapy. Eur Heart J 14 (Suppl C): 24–29, 1993
  • Ju H, Zhao S, Jassal DS, et al. Effect of AT1 receptor blockade on cardiac collagen remodeling after myocardial infarction. Cardiovasc Res 35:223–232, 1997[Abstract/Free Full Text]
  • Briest W, Holzl A, Rassler B, et al. Significance of matrix metalloproteinases in norepinephrine-induced remodelling of rat hearts. Cardiovasc Res 57:379–387, 2003[Abstract/Free Full Text]
  • Langer GA, Frank JS, Philipson KD. Ultrastructure and calcium exchange of the sarcolemma, sarcoplasmic reticulum and mitochondria of the myocardium. Pharmacol Therap 16:331–376, 1982[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Dhalla NS, Ziegelhoffer A, Harrow JA. Regulatory role of membrane systems in heart function. Can J Physiol Pharmacol 55:1211–1234, 1977[ISI][Medline] [Order article via Infotrieve]
  • Carafoli E. The homeostasis of calcium in heart cells. J Mol Cell Cardiol 17:203–212, 1985[ISI][Medline] [Order article via Infotrieve]
  • Dhalla NS, Das PK, Sharma GP. Subcellular basis of cardiac contractile failure. J Mol Cell Cardiol 10:363–385, 1978[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Hess ML. Concise review: Subcellular function in the acutely failing myocardium. Circulatory Shock 6:119–136, 1979[ISI][Medline] [Order article via Infotrieve]
  • Dhalla NS, Pierce GN, Panagia V, et al. Calcium movements in relation to heart function. Basic Res Cardiol 77:117–139, 1982[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Carafoli E, Bing RJ. Myocardial failure. J Appl Cardiol 3:3–18, 1988
  • Dhalla NS, Dixon IM, Beamish RE. Biochemical basis of heart function and contractile failure. J Appl Cardiol 6:7–30, 1991
  • Dhalla NS, Wang X, Beamish RE. Intracellular calcium handling in normal and failing hearts. Exp Clin Cardiol 1:7-7, 1996
  • Davies CH, Harding SE, Poole-Wilson PA. Cellular mechanisms of contractile dysfunction in human heart failure. Eur Heart J 17:189–198, 1996[Free Full Text]
  • Palermo J, Gulick J, Colbert M, et al. Transgenic remodeling of the contractile apparatus in the mammalian heart. Circ Res 78:504–509, 1996[Abstract/Free Full Text]
  • Hefti MA, Harder BA, Eppenberger HM, et al. Signaling pathways in cardiac myocyte hypertrophy. J Mol Cell Cardiol 29:2873–2892, 1997[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Gwathmey JK, Slawsky MT, Hajjar RJ, et al. Role of intracellular calcium handling in force-interval relationships of human ventricular myocardium. J Clin Invest 85:1599–1613, 1990[ISI][Medline] [Order article via Infotrieve]
  • Beuckelmann DJ, Nabauer M, Erdmann E. Intracellular calcium handling in isolated ventricular myocytes from patients with terminal heart failure. Circulation 85: 1046–1055, 1992[Abstract/Free Full Text]
  • Bentivegna LA, Ablin LW, Kihara Y, et al. Altered calcium handling in left ventricular pressure-overload hyper-trophy as detected with aequorin in the isolated, perfused ferret heart. Circ Res 69:1538–1545, 1991[Abstract/Free Full Text]
  • Bailey BA, Houser SR. Calcium transients in feline left ventricular myocytes with hypertrophy induced by slow progressive pressure overload. J Mol Cell Cardiol 24:365–373, 1992[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Bing OH, Brooks WW, Conrad CH, et al. Intracellular calcium transients in myocardium from spontaneously hypertensive rats during the transition to heart failure. Circ Res 68:1390–1400, 1991[Abstract/Free Full Text]
  • Siri FM, Krueger J, Nordin C, et al. Depressed intracellular calcium transients and contraction in myocytes from hypertrophied and failing guinea pig hearts. Am J Physiol Heart Circ Physiol 261:H514–H530, 1991[Abstract/Free Full Text]
  • Pieske B, Sutterlin M, Schmidt-Schweda S, et al. Diminished post-rest potentiation of contractile force in human dilated cardiomyopathy. Functional evidence for alterations in intracellular Ca2+ handling. J Clin Invest 98:764–776, 1996[ISI][Medline] [Order article via Infotrieve]
  • Chang KC, Schreur JH, Weiner MW, et al. Impaired Ca2+handling is an early manifestation of pressure-overload hypertrophy in rat hearts. Am J Physiol Heart Circ Physiol 271:H228–H234, 1996[Abstract/Free Full Text]
  • Dhalla NS, Shao Q, Panagia V. Remodeling of cardiac membranes during the development of congestive heart failure. Heart Failure Reviews 2:261–272, 1998
  • Movsesian MA, Schwinger RH. Calcium sequestration by the sarcoplasmic reticulum in heart failure. Cardiovasc Res 37:352–359, 1998[Free Full Text]
  • Matsui H, MacLennan DH, Alpert NR, et al. Sarcoplasmic reticulum gene expression in pressure overloadinduced cardiac hypertrophy in rabbit. Am J Physiol Cell Physiol 268:C252–C258, 1995[Abstract/Free Full Text]
  • Kiss E, Ball NA, Kranias EG, et al. Differential changes in cardiac phospholamban and sarcoplasmic reticular Ca2+-ATPase protein levels. Effects on Ca2+ transport and mechanics in compensated pressure-overload hypertrophy and congestive heart failure. Circ Res 77:759–764, 1995[Abstract/Free Full Text]
  • Feldman AM, Weinberg EO, Ray PE, et al. Selective changes in cardiac gene expression during compensated hypertrophy and the transition to cardiac decompensation in rats with chronic aortic banding. Circ Res 73:184–192, 1993[Abstract]
  • Zarain-Herzberg A, Rupp H, Elimban V, et al. Modifi-cation of sarcoplasmic reticulum gene expression in pressure overload cardiac hypertrophy by etomoxir. FASEB J 10:1303–1309, 1996[Abstract]
  • Ohkusa T, Hisamatsu Y, Yano M, et al. Altered cardiac mechanism and sarcoplasmic reticulum function in pressure overload-induced cardiac hypertrophy in rats. J Mol Cell Cardiol 29:45–54, 1997[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Hisamatsu Y, Ohkusa T, Kihara Y, et al. Early changes in the functions of cardiac sarcoplasmic reticulum in volume-overloaded cardiac hypertrophy in rats. J Mol Cell Cardiol 29:1097–1109, 1997[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Keller E, Bond M, Moravec CS. Progression of left ventricular hypertrophy does not change the sarcoplasmic reticulum calcium store in the spontaneously hypertensive rat heart. J Mol Cell Cardiol 29:461–469, 1997[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Schwinger RHG, Böhm M, Schmidt U, et al. Unchanged protein levels of SERCA II and phospholamban but reduced Ca2+ uptake and Ca2+-ATPase activity of cardiac sarcoplasmic reticulum from dilated cardiomyopathy patients compared with patients with nonfailing hearts. Circulation 92:3220–3228, 1995[Abstract/Free Full Text]
  • Schlotkhauer K, Scattmann J, Bers DM, et al. Frequency-dependent changes in contribution of SR Ca2+ to Ca2+transients in failing human myocardium assessed with ryanodine. J Mol Cell Cardiol 30:1285–1294, 1998[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Linck B, Boknik P, Eschenhagen T, et al. Messenger RNA expression and immunological quantification of phospholamban and SR-Ca2+-ATPase in failing and nonfailing human hearts. Cardiovasc Res 31:625–632, 1996[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Meyer M, Schillinger W, Pieske B, et al. Alterations of sarcoplasmic reticulum proteins in failing human dilated cardiomyopathy. Circulation 92:778–784, 1995[Abstract/Free Full Text]
  • Hasenfuss G, Reinecke H, Studer R, et al. Relation between myocardial function and expression of sarcoplasmic reticulum Ca2+-ATPase in failing and nonfailing human myocardium. Circ Res 75:434–442, 1994[Abstract/Free Full Text]
  • Arai M, Matsui H, Perisamy M. Sarcoplasmic reticulum gene expression in cardiac hypertrophy and heart failure. Circ Res 74:555–564, 1994[Free Full Text]
  • Gupta RC, Shimoyama H, Tanimura M, et al. SR Ca2+-ATPase activity and expression in ventricular myocardium of dogs with heart failure. Am J Physiol Heart Circ Physiol 273:H12–H18, 1997[Abstract/Free Full Text]
  • Igarashi-Saito K, Tsutsui H, Yamamoto S, et al. Role of SR Ca2+-ATPase in contractile dysfunction of myocytes in tachycardia-induced heart failure. Am J Physiol Heart Circ Physiol 275:H31–H40, 1998[Abstract/Free Full Text]
  • Prestle J, Dieterich S, Preuss M, et al. Heterogeneous transmural gene expression of calcium-handling proteins and natriuretic peptides in the failing human heart. Cardiovasc Res 43:323–331, 1999[Abstract/Free Full Text]
  • Pennock GD, Spooner PH, Summers CE, et al. Prevention of abnormal sarcoplasmic reticulum calcium transport and protein expression in post-infarction heart failure using 3, 5-diiodothyropropionic acid (DITPA). J Mol Cell Cardiol 32:1939–1953, 2000[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Nediani C, Formigli Ll, Perna AM, et al. Early changes induced in the left ventricle by pressure overload. An experimental study on swine heart. J Mol Cell Cardiol 32:131–142, 2000[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Shannon TR, Pogwizd SM, Bers DM. Elevated sarcoplasmic reticulum Ca2+ leak in intact ventricular myocytes from rabbits in heart failure. Circ Res 93:592–594, 2003[Abstract/Free Full Text]
  • Gupta RC, Mishra S, Rastogi S, et al. Cardiac SR-coupled PP1 activity and expression are increased and inhibitor 1 protein expression is decreased in failing hearts. Am J Physiol Heart Circ Physiol 285: H2373–H2381, 2003[Abstract/Free Full Text]
  • Schwinger RHG, Bundgaard Muller-Ehmsen J, et al. The Na, K-ATPase in the failing human heart. Cardiovasc Res 57:913–920, 2003[Abstract/Free Full Text]
  • Verdonck F, Volders PG, Voss MA, et al. Intracellular Na+and altered Na+ transport mechanisms in cardiac hyper-trophy and failure. J Mol Cell Cardiol 35:5–25, 2003[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Despa S, Islam MA, Weber CR, et al. Intracellular Na(+) concentration is elevated in heart failure but Na/K pump function is unchanged. Circulation 105:2543–2548, 2002[Abstract/Free Full Text]
  • Schwinger RH, Wang J, Frank K, et al. Reduced sodium pump alpha1, alpha3, and beta1-isoform protein levels and Na+,K+-ATPase activity but unchanged Na+-Ca2+exchanger protein levels in human heart failure. Circulation 99:2105–2112, 1999[Abstract/Free Full Text]
  • Gomez AM, Schwaller B, Porzig H, et al. Increased exchange current but normal Ca2+ transport via Na+-Ca2+exchange during cardiac hypertrophy after myocardial infarction. Circ Res 91:323–330, 2002[Abstract/Free Full Text]
  • Book CB, Wilson RP, Ng Y-C. Cardiac hypertrophy in the ferret increases expression of the Na+-K+-ATPase alpha 1-but not alpha 3-isoform. Am J Physiol Heart Circ Physiol 266:H1221–H1227, 1994[Abstract/Free Full Text]
  • Sweadner KJ, Herrera VL, Amato S, et al. Immunologic identification of Na+,K+-ATPase isoforms in myocardium. Isoform change in deoxycorticosterone acetate-salt hypertension. Circ Res 74:669–678, 1994[Abstract/Free Full Text]
  • Azuma KK, Hensley CB, Putnam DS, et al. Hypokalemia decreases Na+-K+-ATPase alpha 2-but not alpha 1-iso-form abundance in heart, muscle, and brain. Am J Physiol Cell Physiol 260:C958–C964, 1991[Abstract/Free Full Text]
  • Allen PD, Schmidt TA, Marsh JD, Kjeldsen K. Na,KATPase expression in normal and failing human left ventricle. Basic Res Cardiol 87 (Suppl):87–94, 1992[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Spinale FG, Clayton C, Tanaka R, et al. Myocardial Na+,K+-ATPase in tachycardia induced cardiomyopathy. J Mol Cell Cardiol 24:277–294, 1992[ISI][Medline] [Order article via Infotrieve]
  • Book CBS, Moore RL, Semanchik A, et al. Cardiac hypertrophy alters expression of Na+,K+-ATPase subunit isoforms at mRNA and protein levels in rat myocardium. J Mol Cell Cardiol 26:591–600, 1994[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Ming Z, Nordin C, Siri F, et al. Reduced calcium current density in single myocytes isolated from hypertrophied failing guinea pig hearts. J Mol Cell Cardiol 26: 1133–1143, 1994[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Rannou F, Sainte-Beuve C, Oliviero P, et al. The effects of compensated cardiac hypertrophy on dihydropyridine and ryanodine receptors in rat, ferret and guinea-pig hearts. J Mol Cell Cardiol 27:1225–1234, 1995[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Studer R, Reinecke H, Bilger J, et al. Gene expression of the cardiac Na+-Ca2+ exchanger in end-stage human heart failure. Circ Res 75:443–453, 1994[Abstract/Free Full Text]
  • Moalic JM, Charlemagne D, Mansier P, et al. Cardiac hypertrophy and failure—a disease of adaptation. Modifications in membrane proteins provide a molecular basis for arrhythmogenicity. Circulation 87 (Suppl IV): 21–26, 1993
  • Eble DM, Walker JD, Mukherjee R, et al. Myosin heavy chain synthesis is increased in a rabbit model of heart failure. Am J Physiol Heart Circ Physiol 272:H969–H978, 1997[Abstract/Free Full Text]
  • Kuang SQ, Yu JD, Lu L, et al. Identification of a novel missense mutation in the cardiac beta-myosin heavy chain gene in a Chinese patient with sporadic hypertrophic cardiomyopathy. J Mol Cell Cardiol 28:1879–1883, 1996[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Hasenfuss G, Mulieri LA, Leavitt BJ, et al. Contractile protein function in failing and nonfailing human myocardium. Basic Res Cardiol 87 (Suppl 1):107–116, 1992[Medline] [Order article via Infotrieve]
  • Eble DM, Spinale FG. Contractile and cytoskeletal content, structure, and mRNA levels with tachycardiainduced cardiomyopathy. Am J Physiol Heart Circ Physiol 268:H2426–H2439, 1995[Abstract/Free Full Text]
  • Swoap SJ, Haddad F, Bodell P, et al. Control of beta-myosin heavy chain expression in systemic hypertension and caloric restriction in the rat heart. Am J Physiol Cell Physiol 269:C1025–C1033, 1995[Abstract/Free Full Text]
  • Imamura T, McDermott PJ, Kent RL, et al. Acute changes in myosin heavy chain synthesis rate in pressure versus volume overload. Circ Res 75:418–425, 1994[Abstract/Free Full Text]
  • Rupp H, Elimban V, Dhalla NS. Modification of subcellular organelles in pressure-overloaded heart by etomoxir, a carnitine palmitoyltransferase I inhibitor. FASEB J 6:2349–2353, 1992[Abstract]
  • Toffolo RL, Ianuzzo CD. Myofibrillar adaptations during cardiac hypertrophy. Mol Cell Biochem 131:141–149, 1994[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Schwartz K. Contractile protein gene expression in the hypertrophied heart. Can J Cardiol 9 (Suppl F):12–16, 1993[Medline] [Order article via Infotrieve]
  • Liu LM, Kato M, Takeda N. Alterations of myosin isoenzymes and ADP/ATP carrier in Goldblatt hypertensive rats. Exp Clin Cardiol 2:199–203, 1997
  • Sobieszek A. Regulation of myosin light chain kinase: Kinetic mechanism, autophosphorylation, and cooperative activation by Ca2+ and calmodulin. Can J Physiol Pharmacol 72:1368–1376, 1994[ISI][Medline] [Order article via Infotrieve]
  • Morano I, Hadicke K, Grom S, et al. Titin, myosin light chains and C-protein in the developing and failing human heart. J Mol Cell Cardiol 26:361–368, 1994[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Morano I, Hadlicke K, Haase H, et al. Changes in essential myosin light chain isoform expression provide a molecular basis for isometric force regulation in the failing human heart. J Mol Cell Cardiol 29:1177–1187, 1997[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Cumming DV, Seymour AM, Rix LK, et al. Troponin I and T protein expression in experimental cardiac hyper-trophy. Cardioscience 6:65–70:1995[ISI][Medline] [Order article via Infotrieve]
  • Anderson PA, Greig A, Mark TM, et al. Molecular basis of human cardiac troponin T isoforms expressed in the developing, adult, and failing heart. Circ Res 76:681–686, 1995[Abstract/Free Full Text]
  • Mesnard L, Logeart D, Taviaux S, et al. Human cardiac troponin T: Cloning and expression of new isoforms in the normal and failing heart. Circ Res 76:687–692, 1995[Abstract/Free Full Text]
  • Ravkilde J, Nissen H, Horder M, et al. Independent prognostic value of serum creatine kinase isoenzyme MB mass, cardiac troponin T and myosin light chain levels in suspected acute myocardial infarction. Analysis of 28 months of follow-up in 196 patients. J Am Coll Cardiol 25:574–581, 1995[Abstract]
  • Chen Z, Higashiyama A, Yaku H, et al. Altered expression of troponin T isoforms in mild left ventricular hypertrophy in the rabbit. J Mol Cell Cardiol 29:2345–2354, 1997[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Townsend PJ, Barton PJ, Yacoub MH, et al. Molecular cloning of human cardiac troponin T isoforms: Expression in developing and failing heart. J Mol Cell Cardiol 27:2223–2236, 1995[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Solaro RJ, Burkart EM. Functional defects in troponin and the systems biology of heart failure. J Mol Cell Cardiol 34:689–693, 2002[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Torrealba JR, Lozano E, Griffin M, et al. Maximal ATPase activity and calcium sensitivity of reconstituted myofilaments are unaltered by the fetal troponin T re-expressed during human heart failure. J Mol Cell Cardiol 34:797–805, 2002[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Lindpaintner K, Ganten D. The cardiac renin-angiotensin system. An appraisal of present experimental and clinical evidence. Circ Res 68:905–921, 1991
  • Lindpaintner K, Niedermaier N, Drexler H, et al. Left ventricular remodeling after myocardial infarction: Does the cardiac renin-angiotensin system play a role? J Cardiovas Pharmacol 20 (Suppl 1):S41–S47, 1992
  • Basu S, Sinha SK, Shao Q, et al. Neuropeptide Y modulation of sympathetic activity in myocardial infarction. Am J Coll Cardiol 27:1796–1803, 1996[Abstract]
  • Dostal DE, Baker KM. The cardiac renin-angiotensin system: Conceptual, or a regulator of cardiac function? Circ Res 85:643–650, 1999[Abstract/Free Full Text]
  • Lijnen P, Petrov V. Renin-angiotensin system, hypertrophy and gene expression in cardiac myocytes. J Mol Cell Cardiol 31:949–970, 1999[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Dostal DE. The cardiac renin-angiotensin system: Novel signaling mechanisms related to cardiac growth and function. Regulatory Peptides 91:1–11, 2000[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Kim S, Iwao H. Molecular and cellular mechanisms of angiotensin II-mediated cardiovascular and renal diseases. Pharmacol Rev 52:11–34, 2000[Abstract/Free Full Text]
  • Hu LW, Benvenuti LA, Liberti EA, et al. Thyroxine-induced cardiac hypertrophy: Influence of adrenergic nervous system versus renin-angiotensin system on myocyte remodeling. Am J Physiol Regul Integ Comp Physiol 285: R1473–R1480, 2003[Abstract/Free Full Text]
  • Wang X, Dhalla NS. Modification of beta-adrenoceptor signal transduction pathway by genetic manipulation and heart failure. Mol Cell Biochem 214:131–155, 2000[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Ju H, Scammel-LaFleur T, Dixon IM. Altered mRNA abundance of calcium transport genes in cardiac myocytes induced by angiotensin II. J Mol Cell Cardiol 28:1119–1128, 1996[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Shizukuda Y, Buttrick PM, Geenen DL, et al. Beta-adrenergic stimulation causes cardiocyte apoptosis: Influence of tachycardia and hypertrophy. Am J Physiol Heart Circ Physiol 275:H961–H968, 1998[Abstract/Free Full Text]
  • Linck B, Boknik P, Baba HA, et al. Long-term beta adrenoceptor-mediated alteration in contractility and expression of phospholamban and sarcoplasmic reticulum Ca2+-ATPase in mammalian ventricle. J Pharmacol Exp Therap 286:531–538, 1998[Abstract/Free Full Text]
  • Lai LP, Raju VS, Delehanty JM, et al. Altered sarcoplasmic reticulum Ca2+ ATPase gene expression in congestive heart failure: Effect of chronic norepinephrine infusion. J Mol Cell Cardiol 30:175–185, 1998[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Gu X, Bishop SP. Increased protein kinase C and isozyme redistribution in pressure-overload cardiac hypertrophy in the rat. Circ Res 75:926–931, 1994[Abstract/Free Full Text]
  • Hartong R, Villarreal FJ, Giordano F, et al. Phorbol myris-tate acetate-induced hypertrophy of neonatal rat cardiac myocytes is associated with decreased sarcoplasmic reticulum Ca2+ ATPase (SERCA2) gene expression and calcium reuptake. J Mol Cell Cardiol 28:2467–2477, 1996[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Rouet-Benzineb P, Gontero B, Dreyfuss P, et al. Angiotensin II induces nuclear factor-kappa B activation in cultured neonatal rat cardiomyocytes through protein kinase C signaling pathway. J Mol Cell Cardiol 32:1767–1778, 2000[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Takeishi Y, Bhagwat A, Ball NA, et al. Effect of angiotensin-converting enzyme inhibition on protein kinase C and SR proteins in heart failure. Am J Physiol Heart Circ Physiol 276:H53–H63, 1999[Abstract/Free Full Text]
  • Baines CP, Song C-X, Zheng YT, et al. Protein kinase Cepsilon interacts with and inhibits the permeability transition pore in cardiac mitochondria. Circ Res 92:873–880, 2003[Abstract/Free Full Text]
  • English JM, Cobb MH. Pharmacological inhibitors of MAPK pathways. Trends Pharmacol Sci 23:40–45, 2002[CrossRef][Medline] [Order article via Infotrieve]
  • Hagemann C, Blank JL. The ups and downs of MEK kinase interactions. Cell Signaling 13:863–875, 2003
  • Force T, Pombo CM, Avruch J, et al. Stress-activated protein kinases in cardiovascular disease. Circ Res 78:947–953, 1996[Free Full Text]
  • Dhalla NS, Dixon IM, Rupp H, et al. Experimental congestive heart failure due to myocardial infarction: Sarcolemmal receptors and cation transporters. Basic Res Cardiol 86 (Suppl. 3):13–23, 1991
  • Cheng TO. Cardiac failure in coronary heart disease. Am Heart J 120:396–412, 1990[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Lerman RH, Apstein CS, Kagan HS, et al. Myocardial healing and repair after experimental infarction in the rabbit. Circ Res 53:378–388, 1983[Abstract/Free Full Text]
  • Cox MM, Berman I, Myerburg RJ, et al. Morphometric mapping of regional myocyte diameters after healing of myocardial infarction in cats. J Mol Cell Cardiol 23:127–135, 1991[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Vanoli E, De Ferrari GM, Stramba-Badiale M, et al. Vagal stimulation and prevention of sudden death in conscious dogs with a healed myocardial infarction. Circ Res 68:1471–1481, 1991[Abstract/Free Full Text]
  • Sabbah HN, Kono T, Stein PD, et al. Left ventricular shape changes during the course of evolving heart failure. Am J Physiol Heart Circ Physiol 263:H266–H270, 1992[Abstract/Free Full Text]
  • McDonald KM, Francis GS, Carlyle PF, et al. Hemo-dynamic, left ventricular structural and hormonal changes after discrete myocardial damage in the dog. J Am Coll Cardiol 19:460–467, 1992[Abstract]
  • Jugdutt BI, Schwarz-Michorowski BL, Khan MI. Effect of long-term captopril therapy on left ventricular remodeling and function during healing of canine myocardial infarction. J Am Coll Cardiol 19:713–721, 1992[Abstract]
  • Connelly CM, Ngoy S, Schoen FJ, et al. Biomechanical properties of reperfused transmural myocardial infarcts in rabbits during the first week after infarction. Implications for left ventricular rupture. Circ Res 71:401–413, 1992[Abstract/Free Full Text]
  • Knowlton AA, Connelly CM, Romo GM, et al. Rapid expression of fibronectin in the rabbit heart after myocardial infarction with and without reperfusion. J Clin Invest 89:1060–1068, 1992[ISI][Medline] [Order article via Infotrieve]
  • Kozlovskis PL, Gerdes AM, Smets M, et al. Regional increase in isolated myocyte volume in chronic myocardial infarction in cats. J Mol Cell Cardiol 23:1459–1466, 1991[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Johns TN, Olson BJ. Experimental myocardial infarction. I. A method of coronary occlusion in small animals. Ann Surg 140:675–682, 1954
  • Selye H, Bajusz E, Grasso S, et al. Simple techniques for the surgical occlusion of coronary vessels in the rat. Angiology 11:398–407, 1960[Free Full Text]
  • Fishbein MC, Maclean D, Maroko PR. Experimental myocardial infarction in the rat: Qualitative and quantitative changes during pathologic evolution. Am J Pathol 90:57–70, 1978[Abstract]
  • Pfeffer MA, Pfeffer JM, Fishbein MC, et al. Myocardial infarct size and ventricular function in rats. Circ Res 44:503–512, 1979[Abstract/Free Full Text]
  • Geenen DL, Malhotra A, Liang D, et al. Ventricular function and contractile proteins in the infarcted overloaded rat heart. Cardiovasc Res 25:330–336, 1991[Abstract/Free Full Text]
  • Gopalakrishnan M, Triggle DJ, Rutledge A, et al. Regulation of K+ and Ca2+ channels in experimental cardiac failure. Am J Physiol Heart Circ Physiol 261: H1979–H1987, 1991[Abstract/Free Full Text]
  • Chasteney EA, Liang CS, Hood WB Jr. Beta-adrenoceptor and adenylate cyclase function in the infarct model of rat heart failure. Proc Soc Exp Biol Med 200:90–94, 1992[Abstract]
  • Qi XL, Stewart DJ, Gosselin H, et al. Improvement of endocardial and vascular endothelial function on myocardial performance by captopril treatment in postinfarct rat hearts. Circulation 100:1338–1345, 1999[Abstract/Free Full Text]
  • Rowley KG, Tung LH, Hodsman GP, et al. Altered alpha 1-adrenoceptor-mediated responses in atria of rats with chronic left ventricular infarction. J Cardiovasc Pharmacol 17:474–479, 1991[ISI][Medline] [Order article via Infotrieve]
  • Rubin SA, Fishbein MC, Swan HJ. Compensatory hyper-trophy in the heart after myocardial infarction in the rat. J Am Coll Cardiol 1:1435–1441, 1983[Abstract]
  • Anversa P, Beghi C, Kikkawa Y, et al. Myocardial infarction in rats. Infarct size, myocyte hypertrophy, and capillary growth. Circ Res 58:26–37, 1986[Abstract/Free Full Text]
  • Anversa P, Beghi C, McDonald SL, et al. Morphometry of right ventricular hypertrophy induced by myocardial infarction in the rat. Am J Pathol 116:504–513, 1984[Abstract]
  • Zimmer HG, Gerdes AM, Lortet S, et al. Changes in heart function and cardiac cell size in rats with chronic myocardial infarction. J Mol Cell Cardiol 22:1231–1243, 1990[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Fletcher PJ, Pfeffer JM, Pfeffer MA, et al. Left ventricular diastolic pressure-volume relations in rats with healed myocardial infarction. Effects on systolic function. Circ Res 49:618–626, 1981[Abstract/Free Full Text]
  • Pfeffer JM, Pfeffer MA, Fletcher PJ, et al. Ventricular performance in rats with myocardial infarction and failure. Am J Med 76:99–103, 1984[Medline] [Order article via Infotrieve]
  • DeFelice A, Frering R, Horan P. Time course of hemodynamic changes in rats with healed severe myocardial infarction. Am J Physiol Heart Circ Physiol 257: H289–H296, 1989[Abstract/Free Full Text]
  • Geenen DL, Malhotra A, Scheuer H. Regional variation in rat cardiac myosin isoenzymes and ATPase activity after infarction. Am J Physiol Heart Circ Physiol 256:H745–H750, 1989[Abstract/Free Full Text]
  • Liu X, Shao Q, Dhalla NS. Myosin light chain phosphorylation in cardiac hypertrophy and failure due to myocardial infarction. J Mol Cell Cardiol 27:2613–2621, 1995[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Akiyama K, Akopian G, Jinadasa P, et al. Myocardial infarction and regulatory myosin light chain. J Mol Cell Cardiol 29:2641–2652, 1997[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Li P, Hofman PA, Li B, et al. Myocardial infarction alters myofilament calcium sensitivity and mechanical behavior of myocytes. Am J Physiol Heart Circ Physiol 272: H360–H370, 1997[Abstract/Free Full Text]
  • Fellenius E, Hansen CA, Mjos O, et al. Chronic infarction decreases maximum cardiac work and sensitivity of heart to extracellular calcium. Am J Physiol Heart Circ Physiol 249:H80–H87, 1985[Abstract/Free Full Text]
  • De Tombe PP, Wannenburg T, Fan D, et al. Right ventricular contractile protein function in rats with left ventricular myocardial infarction. Am J Physiol Heart Circ Physiol 271:H73–H79, 1996[Abstract/Free Full Text]
  • Buttrick P, Perla C, Maholtra A, et al. Effects of chronic dobutamine on cardiac mechanics and biochemistry after myocardial infarction in rats. Am J Physiol Heart Circ Physiol 260:H473–H479, 1991[Abstract/Free Full Text]
  • Drexler H, Depenbusch JW, Truog AG, et al. Effects of diltiazem on cardiac function and regional blood flow at rest and during exercise in a conscious rat preparation of chronic heart failure (myocardial infarction). Circulation 71:1262–1270, 1985[Abstract/Free Full Text]
  • Pelouch V, Dixon IM, Sethi R, et al. Alteration of collagenous protein profile in congestive heart failure secondary to myocardial infarction. Mol Cell Biochem 129: 121–131, 1994
  • Lui K, Jackson M, Sowa MG, et al. Modification of the extracellular matrix following myocardial infarction monitored by FTIR spectroscopy. Biochim Biophys Acta 1315:73–77, 1996[Medline] [Order article via Infotrieve]
  • Gallagher AM, Omens JH, Chu LL, et al. Alterations in collagen fibrillar structure and mechanical properties of the healing scar following myocardial infarction. Cardiovasc Pathobiol 1:25–36, 1997
  • Eberli FR, Sam F, Ngoy S, et al. Left-ventricular structural and functional remodeling in the mouse after myocardial infarction: Assessment with the isovolumetricallycontracting Langendorff heart. J Mol Cell Cardiol 30:1443–1447, 1998[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Gosselin H, Qi X, Rouleau JL. Correlation between cardiac remodelling, function, and myocardial contractility in rat hearts 5 weeks after myocardial infarction. Can J Physiol Pharmacol 76:53–62, 1998[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Siminiak T, Smielecki J, Dye JF, et al. Detection of the soluble adhesion molecules L-selectin and vascular cell adhesion molecule 1 during acute myocardial infarction. Exp Clin Cardiol 2:215–218, 1997
  • Takemura G, Ohno M, Hayakawa Y, et al. Role of apoptosis in the disappearance of infiltrated and proliferated interstitial cells after myocardial infarction. Circ Res 82:1130–1138, 1998[Abstract/Free Full Text]
  • Litwin SE, Raya TE, Anderson PG, et al. Induction of myocardial hypertrophy after coronary ligation in rats decreases ventricular dilatation and improves systolic function. Circulation 84:1819–1827, 1991[Abstract/Free Full Text]
  • Ganguly PK, Dhalla KS, Shao Q, et al. Differential changes in sympathetic activity in left and right ventricles in congestive heart failure after myocardial infarction. Am Heart J 133:340–345, 1997[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Oie E, Bjonerheim R, Grogaard HK, et al. ET-receptor antagonism, myocardial gene expression, and ventricular remodeling during CHF in rats. Am J Physiol Heart Circ Physiol 275:H868–H877, 1998[Abstract/Free Full Text]
  • Kramer JH, Phillips TM, Weglicki WB. Magnesium-deficiency-enhanced post-ischemic myocardial injury is reduced by substance P receptor blockade. J Mol Cell Cardiol 29:97–110, 1997[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Ontkean M, Gay R, Greenberg B. Diminished endothelium-derived relaxing factor activity in an experimental model of chronic heart failure. Circ Res 69:1088–1096, 1991[Abstract/Free Full Text]
  • Mendez RE, Pfeffer JM, Ortola FV, et al. Atrial natriuretic peptide transcription, storage, and release in rats with myocardial infarction. Am J Physiol Heart Circ Physiol 253:H1449–H1455, 1987[Abstract/Free Full Text]
  • Drexler H, Hirth C, Stasch HP, et al. Vasodilatory action of endogenous atrial natriuretic factor in a rat model of chronic heart failure as determined by monoclonal ANF antibody. Circ Res 66:1371–1380, 1990[Abstract/Free Full Text]
  • Hodsman GP, Kohzuki M, Howes LG, et al. Neurohumoral responses to chronic myocardial infarction in rats. Circulation 78:376–381, 1988[Abstract/Free Full Text]
  • Tsunoda K, Hodsman GP, Sumithran E, et al. Atrial natriuretic peptide in chronic heart failure in the rat: A correlation with ventricular dysfunction. Circ Res 59:256–261, 1986[Abstract/Free Full Text]
  • Shao Q, Takeda N, Temsah R, et al. Prevention of hemo-dynamic changes due to myocardial infarction by early treatment of rats with imidapril. Cardiovasc Pathobiol 1:180–186, 1996
  • Dixon IM, Lee SL, Dhalla NS. Nitrendipine binding in congestive heart failure due to myocardial infarction. Circ Res 66:782–788, 1990[Abstract/Free Full Text]
  • Afzal N, Dhalla NS. Differential changes in left and right ventricular SR calcium transport in congestive heart failure. Am J Physiol Heart Circ Physiol 262:H868–H874, 1992[Abstract/Free Full Text]
  • Yamaguchi F, Sanbe A, Takeo S. Cardiac sarcoplasmic reticular function in rats with chronic heart failure following myocardial infarction. J Mol Cell Cardiol 29: 753–763, 1997[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Afzal N, Dhalla NS. Sarcoplasmic reticular Ca2+ pump ATPase activity in congestive heart failure due to myocardial infarction. Can J Cardiol 12:1065–1073, 1996[ISI][Medline] [Order article via Infotrieve]
  • Zarain-Herzberg A, Afzal N, Elimban V, et al. Decreased expression of cardiac sarcoplasmic reticulum Ca2+-pump ATPase in congestive heart failure due to myocardial infarction. Mol Cell Biochem 163/164:285–290, 1996
  • Yoshiyama M, Takeuchi K, Hanatani A, et al. Differences in expression of sarcoplasmic reticulum Ca2+-ATPase and Na+-Ca2+ exchanger genes between adjacent and remote noninfarcted myocardium after myocardial infarction. J Mol Cell Cardiol 29:255–264, 1997[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Dixon IM, Dhalla NS. Alterations in cardiac adrenoceptors in congestive heart failure secondary to myocardial infarction. Cor Art Disease 2:805–814, 1991
  • Sethi R, Dhalla KS, Beamish RE, et al. Differential changes in left and right ventricular adenylyl cyclase activities in congestive heart failure. Am J Physiol Heart Circ Physiol 272:H884–H893, 1997[Abstract/Free Full Text]
  • Dixon IM, Hata T, Dhalla NS. Sarcolemmal Na+-K+-ATPase activity in congestive heart failure due to myocardial infarction. Am J Physiol Cell Physiol 262: C664–C671, 1992[Abstract/Free Full Text]
  • Semb SO, Lunde PK, Holt E, et al. Reduced myocardial Na+, K+-pump capacity in congestive heart failure following myocardial infarction in rats. J Mol Cell Cardiol 30:1311–1328, 1998[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Dixon IM, Hata T, Dhalla NS. Sarcolemmal calcium transport in congestive heart failure due to myocardial infarction in rats. Am J Physiol Heart Circ Physiol 262:H1387–H1394, 1992[Abstract/Free Full Text]
  • Anand IS, Liu D, Chugh SS, et al. Isolated myocyte contractile function is normal in postinfarct remodeled rat heart with systolic dysfunction. Circulation 96:3974–3984, 1997[Abstract/Free Full Text]
  • Kiseleva I, Kamkin A, Pylaev A, et al. Electrophysiological properties of mechanosensitive atrial fibroblasts from chronic infarcted rat heart. J Mol Cell Cardiol 30:1083–1093, 1998[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Zhang X-Q, Moore RL, Tillottson DL, et al. Calcium currents in postinfarction rat cardiac myocytes. Am J Physiol Cell Physiol 269:C1464–C1473, 1995[Abstract/Free Full Text]
  • Aggarwal R, Pu J, Boyden PA. Ca2+-dependent outward currents in myocytes from epicardial border zone of 5-day infarcted canine heart. Am J Physiol Heart Circ Physiol 273:H1386–H1394, 1997[Abstract/Free Full Text]
  • Zhang X-Q, Tilloston DL, Moore RL, et al. Na+/Ca2+exchange currents and SR Ca2+ contents in postinfarction myocytes. Am J Physiol Cell Physiol 271:C1800–C1807, 1996[Abstract/Free Full Text]
  • Gidh-Jain M, Huang B, Jain P, et al. Differential expression of voltage-gated K+ channel genes in left ventricular remodeled myocardium after experimental myocardial infarction. Circ Res 79:669–675, 1996[Abstract/Free Full Text]
  • Ren B, Lukas A, Shao Q, et al. Electrocardiographic changes and mortality due to myocardial infarction in rats with or without imidapril treatment. J Cardiovas Pharmacol Therapeut 3:11–22, 1998
  • Schoemaker RG, Debets JJ, Struyker-Boudier HA, et al. Delayed but not immediate captopril therapy improves cardiac function in conscious rats, following myocardial infarction. J Mol Cell Cardiol 23:187–197, 1991
  • Jugdutt BI, Schwarz-Michorowski BL, Khan MI. Effect of long-term captopril therapy on left ventricular remodeling and function during healing of canine myocardial infarction. J Am Coll Cardiol 19:713–721, 1992[Abstract]
  • Dixon IM, Ju H, Jassal DS, et al. Effect of ramipril and losartan on collagen expression in right and left heart after myocardial infarction. Mol Cell Biochem 165:31–45, 1996[ISI][Medline] [Order article via Infotrieve]
  • van Krimpen C, Smits JF, Cleutjens JP, et al. DNA synthesis in the non-infarcted cardiac interstitium after left coronary artery ligation in the rat: Effects of captopril. J Mol Cell Cardiol 23:1245–1253, 1991[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • McDonald KM, Chu C, Francis JS, et al. Effect of delayed intervention with ACE-inhibitor therapy on myocyte hypertrophy and growth of the cardiac interstitium in the rat model of myocardial infarction. J Mol Cell Cardiol 29:3202–3210, 1997
  • Gonzalez W, Beslot F, Laboulandine I, et al. Inhibition of both angiotensin-converting enzyme and neutral endopeptidase by S21402 (RB105) in rats with experimental myocardial infarction. J Pharmacol Exptl Therap 278:573–581, 1996[Abstract/Free Full Text]
  • Kuizinga MC, Smits JF, Arends JW, et al. AT2 receptor blockade reduces cardiac interstitial cell DNA synthesis and cardiac function after rat myocardial infarction. J Mol Cell Cardiol 30:425–434, 1998[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Ford WR, Khan MI, Jugdutt BI. Effect of the novel angiotensin II type 1 receptor antagonist L-158,809 on acute infarct expansion and acute anterior myocardial infarction in the dog. Can J Cardiol 14:73–80, 1998[ISI][Medline] [Order article via Infotrieve]
  • Raya TE, Gay RG, Aguirre M, et al. Importance of venodilatation in prevention of left ventricular dilatation after chronic large myocardial infarction in rats: A comparison of captopril and hydralazine. Circ Res 64:330–337, 1989[Abstract/Free Full Text]
  • Michel JB, Lattion AL, Salzmann JL, et al. Hormonal and cardiac effects of converting enzyme inhibition in rat myocardial infarction. Circ Res 62:641–650, 1988[Abstract/Free Full Text]
  • Wollert KC, Studer R, von Bulow B, et al. Survival after myocardial infarction in the rat. Role of tissue angiotensin-converting enzyme inhibition. Circulation 90:2457–2467, 1994[Abstract/Free Full Text]
  • Liu YH, Yang XP, Sharov VG, et al. Effects of angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor antagonists in rats with heart failure. Role of kinins and angiotensin II type 2 receptors. J Clin Invest 99:1926–1935, 1997[ISI][Medline] [Order article via Infotrieve]
  • Sanbe A, Takeo S. Long-term treatment with angiotensin I-converting enzyme inhibitors attenuates the loss of cardiac beta-adrenoceptor responses in rats with chronic heart failure. Circulation 92:2666–2675, 1995[Abstract/Free Full Text]
  • Litwin SE, Morgan JP. Captopril enhances intracellular calcium handling and beta-adrenergic responsiveness of myocardium from rats with postinfarction failure. Circ Res 71:797–807, 1992[Abstract/Free Full Text]
  • Gay RG, Raya TE, Goldman S. Chronic propranolol treatment promotes left ventricular dilation without altering systolic function after large myocardial infarction in rats. J Cardiovas Pharmacol 16:529–536, 1990[ISI][Medline] [Order article via Infotrieve]
  • Hu K, Gaudron P, Ertl G. Long-term effects of beta-adrenergic blocking agent treatment on hemodynamic function and left ventricular remodeling in rats with experimental myocardial infarction: importance of timing of treatment and infarct size. J Am Coll Cardiol 31:692–700, 1998[Abstract/Free Full Text]
  • Sharpe N. Beta-blockers in heart failure. Future directions. Eur Heart J 17 (Suppl B):39–42, 1996[Medline] [Order article via Infotrieve]
  • Bohm M, Deutsch HJ, Hartmann D, et al. Improvement of postreceptor events by metoprolol treatment in patients with chronic heart failure. J Am Coll Cardiol 30:992–996, 1997[Abstract]
  • Savonitto S, Ardissino D, Egstrup K, et al. Combination therapy with metoprolol and nifedipine versus monotherapy in patients with stable angina pectoris results of the international multicenter angina exercise (IMAGE) study. J Am Coll Cardiol 27:311–316, 1996[Abstract]
  • Fan T-HM, Frantz RP, Elam H, et al. Reductions of myocardial Na-K-ATPase activity and ouabain binding sites in heart failure: Prevention by nadolol. Am J Physiol Heart Circ Physiol 265:H2086–H2093, 1993[Abstract/Free Full Text]
  • Sigmund M, Jakob H, Becker H, et al. Effects of metoprolol on myocardial beta-adrenoceptors and Gi alpha-proteins in patients with congestive heart failure. Eur J Clin Pharmacol 51:127–132, 1996[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Levett JM, Marinelli CC, Lund DD, et al. Effects of beta-blockade on neurohumoral responses and neurochemical markers in pacing-induced heart failure. Am J Physiol Heart Circ Physiol 266:H468–H475, 1994[Abstract/Free Full Text]
  • Levy S. Secondary prevention after myocardial infarction: In favor of beta-blockers. J Cardiovasc Pharmacol 16:S50–S54, 1990
  • Leitch JW, McElduff P, Dobson A, et al. Outcome with calcium channel antagonists after myocardial infarction: A community-based study. J Am Coll Cardiol 31:111–117, 1998[Abstract/Free Full Text]
  • Gilligan DM, Chan WL, Joshi J, et al. A double-blind, placebo-controlled crossover trial of nadolol and vera-pamil in mild and moderately symptomatic hypertrophic cardiomyopathy. J Am Coll Cardiol 21:1672–1679, 1993[Abstract]
  • Liu P. Reappraisal of calcium channel blockers in heart failure. Can J Cardiol 12:9F-13F, 1996